Osteoporosis is a significant concern for both older men and women. Recent studies suggest skeletal biomarkers might provide important information about the biologic causes of osteoporosis and may be useful to predict fracture alone or when combined with other risk factors. To extend his ongoing NIH-funded work on biomarkers and skeletal fragility, Dr. Douglas Bauer, Professor of Medicine, Epidemiology &Biostatistics at the University of California, San Francisco, is requesting a renewal of his K24 Midcareer Investigator Award in Patient-Oriented Research with the scientific goals of developing new and clinically useful proteomic biomarkers using data from a well characterized longitudinal cohort of older men (MrOS). Taking advantage of ongoing assessments for fracture and recent funding for proteomic measurements in serum collected at baseline, this study will explore the prospective relationship between proteomic profile and incident vertebral fracture in 3000 MrOS participants. Using these and other data from multiple large studies available through his longstanding affiliation with the San Francisco Coordinating Center, Dr. Bauer will continue to mentor young investigators who are interested in clinical research, particularly residents. With the initial K24 award Dr. Bauer mentored residents and fellows who are now pursuing additional research training and academic careers. In conjunction with the UCSF Clinical and Translational Science Institute, during the initial K24 award he also developed and directed a new comprehensive Resident Research Program. The goal of this novel program is to promote clinical research careers by providing residents with formal instruction in research methods, pilot funding and opportunities to participate in mentored research projects. The continuation of this K24 award is critical to protect Dr. Bauer's time and allow him to continue to make significant contributions towards patient-oriented research related to biomarkers and skeletal fragility and to expand his successful mentoring program.